Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy

Barbora Malecova, Sole Gatto, Usue Etxaniz, Magda Passafaro, Amy Cortez, Chiara Nicoletti, Lorenzo Giordani, Alessio Torcinaro, Marco De Bardi, Silvio Bicciato, Francesca De Santa, Luca Madaro, Pier Lorenzo Puri

Research output: Contribution to journalArticle

Abstract

Fibro-adipogenic progenitors (FAPs) are currently defined by their anatomical position, expression of non-specific membrane-associated proteins, and ability to adopt multiple lineages in vitro. Gene expression analysis at single-cell level reveals that FAPs undergo dynamic transitions through a spectrum of cell states that can be identified by differential expression levels of Tie2 and Vcam1. Different patterns of Vcam1-negative Tie2high or Tie2low and Tie2low/Vcam1-expressing FAPs are detected during neonatal myogenesis, response to acute injury and Duchenne Muscular Dystrophy (DMD). RNA sequencing analysis identified cell state-specific transcriptional profiles that predict functional interactions with satellite and inflammatory cells. In particular, Vcam1-expressing FAPs, which exhibit a pro-fibrotic expression profile, are transiently activated by acute injury in concomitance with the inflammatory response. Aberrant persistence of Vcam1-expressing FAPs is detected in DMD muscles or upon macrophage depletion, and is associated with muscle fibrosis, thereby revealing how disruption of inflammation-regulated FAPs dynamics leads to a pathogenic outcome.

Original languageEnglish
Article number3670
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy'. Together they form a unique fingerprint.

  • Cite this

    Malecova, B., Gatto, S., Etxaniz, U., Passafaro, M., Cortez, A., Nicoletti, C., Giordani, L., Torcinaro, A., De Bardi, M., Bicciato, S., De Santa, F., Madaro, L., & Puri, P. L. (2018). Dynamics of cellular states of fibro-adipogenic progenitors during myogenesis and muscular dystrophy. Nature Communications, 9(1), [3670]. https://doi.org/10.1038/s41467-018-06068-6